Download the full-sized PDF of Characterization of Phosphatidylcholine Metabolism in Mouse Hepatocytes after Hepatectomy and in Primary Human HepatocytesDownload the full-sized PDF


Download  |  Analytics

Export to: EndNote  |  Zotero  |  Mendeley


This file is in the following communities:

Faculty of Graduate Studies and Research


This file is not currently in any collections.

Characterization of Phosphatidylcholine Metabolism in Mouse Hepatocytes after Hepatectomy and in Primary Human Hepatocytes Open Access


Other title
non-alcoholic fatty liver disease
partial hepatectomy
primary human hepatocytes
liver regeneration
Type of item
Degree grantor
University of Alberta
Author or creator
Ling, Ji
Supervisor and department
Vance, Dennis (Biochemistry)
Examining committee member and department
Cohen, David (Medicine)
Mason, Andrew (Medicine)
Fernandez-Patron, Carlos (Biochemistry)
Lehner, Richard (Pediatrics, Cell Biology)
Department of Biochemistry

Date accepted
Graduation date
Doctor of Philosophy
Degree level
Phosphatidylcholine (PC) is the major component of mammalian membranes and the induction of PC biosynthesis has been shown to be an essential step in cell proliferation in various cell lines. In the liver, PC biosynthesis is regulated by two pathways: the CDP-choline and the phosphatidylethanolamine N-methyltransferase (PEMT) pathways. The major enzymes that regulate these two pathways are CTP:phosphocholine cytidylyltransferase (CT)α and PEMT, respectively. In our first study, we elucidated the role of PC biosynthesis during proliferation by monitoring liver regeneration after 70% partial hepatectomy (PH) in mice lacking hepatic CTα (LCTα-/- mice). In the liver, CDP-choline is the major pathway of PC biosynthesis. To our surprise, liver re-growth, DNA synthesis, and PC mass after surgery were not impaired in LCTα-/- mice despite reduced total PC synthesis. Furthermore, PC synthesis in control mice was not induced after PH. Thus, we concluded that CTα is not essential for hepatocyte proliferation in vivo and that basal hepatic PC biosynthesis is sufficient to sustain regeneration after PH. In the second study, we assessed hepatic PC to phosphatidylethanolamine ratio (PC/PE) as a predictor of non-alcoholic fatty liver disease (NAFLD) and post-operative complications after major hepatectomy. LCTα-/- mice, PEMT-deficient mice (Pemt-/- mice), and their respective controls were fed a high fat diet to induce various degrees of NAFLD, before PH was performed. We found significant correlation of decreased PC/PE (pre-surgery) with the progression of NAFLD and decreased survival rate after PH. Additionally, dietary choline supplementation increased hepatic PC/PE in Pemt-/- mice with NAFLD, decreased inflammation, and increased survival rate after partial hepatectomy. Thus, choline supplementation may serve as a potential therapy to prevent the progression of NAFLD and to improve post-operative outcome after liver surgery. Finally, we characterized some fundamental aspects of lipid and lipoprotein metabolism in primary human hepatocytes. In particular, we evaluated the synthesis of phospholipids in relation to lipoprotein metabolism. Overall, this work has contributed to the understanding of important processes required for liver regeneration as well as discovering the similarities and differences in lipid and lipoprotein metabolism in primary human hepatocytes compared to hepatoma cell lines and rodent primary hepatocytes.
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
Citation for previous publication

File Details

Date Uploaded
Date Modified
Audit Status
Audits have not yet been run on this file.
File format: pdf (Portable Document Format)
Mime type: application/pdf
File size: 7141399
Last modified: 2015:10:12 11:25:43-06:00
Filename: Ji Ling Spring 2012.pdf
Original checksum: 9b24c744c859553d48b74fb126194d8b
Well formed: true
Valid: true
Page count: 257
Activity of users you follow
User Activity Date